A high-protein diet lowers blood glucose postprandially in persons with type 2 diabetes and improves overall glucose control. However, longer-term studies are necessary to determine the total magnitude of response, possible adverse effects, and the long-term acceptability of the diet.

There has been interest in the effect of various types and amounts of dietary carbohydrates and proteins on blood glucose. On the basis of our previous data, we designed a high-protein/low-carbohydrate, weight-maintaining, nonketogenic diet. Its effect on glucose control in people with untreated type 2 diabetes was determined. We refer to this as a low-biologically-availableglucose (LoBAG) diet. Eight men were studied using a randomized 5-week crossover design with a 5-week washout period. The carbohydrate:protein:fat ratio of the control diet was 55:15:30. The test diet ratio was 20:30:50. Plasma and urinary ␤-hydroxybutyrate were similar on both diets. The mean 24-h integrated serum glucose at the end of the control and LoBAG diets was 198 and 126 mg/dl, respectively. The percentage of glycohemoglobin was 9.8 ؎ 0.5 and 7.6 ؎ 0.3, respectively. It was still decreasing at the end of the LoBAG diet. Thus, the final calculated glycohemoglobin was estimated to be ϳ6.3-5.4%. Serum insulin was decreased, and plasma glucagon was increased. Serum cholesterol was unchanged. Thus, a LoBAG diet ingested for 5 weeks dramatically reduced the circulating glucose concentration in people with untreated type 2 diabetes. Potentially, this could be a patient-empowering way to ameliorate hyperglycemia without pharmacological intervention. The long-term effects of such a diet remain to be determined. Diabetes 53:2375-2382, 2004 D ata obtained in our laboratory (1-3) as well as from others (reviewed in 4) indicate that glucose that is absorbed after the digestion of glucose-containing foods is largely responsible for the rise in the circulating glucose concentration after ingestion of mixed meals. Dietary proteins, fats, and absorbed fructose and galactose resulting from the digestion of sucrose and lactose, respectively, have little effect on blood glucose concentration.We and others also have reported that even short-term starvation (hours) results in a dramatic decrease in the blood glucose concentration in people with type 2 diabetes (5). This seems to be due largely to a rapid, progressive decrease in the rate of glycogenolysis (5,6). Hepatic glycogen stores in turn are dependent on the content of carbohydrate in the diet (6). Thus, a reduced-carbohydrate diet should result in a lower overnight fasting glucose concentration.To test the hypothesis that a diet that is low in carbohydrate and particularly low in food-derived glucose could lower both the fasting and the postprandial blood glucose in people with type 2 diabetes, we designed a lowcarbohydrate diet in which readily digestible starch-containing foods have been de-emphasized. However, the carbohydrate content is sufficient to prevent ketosis. This is in contrast to the low-carbohydrate diets being advocated for weight loss (7). We refer to this as a lowbiologically-available-glucose (LoBAG) diet. In our study, we also attempted to ensure weight stability. The effect of 5 weeks of this diet on percentage glycohemoglobin and 24-h glucose, insulin, C-peptide, ␤-hydroxybuty...

Type II diabetic subjects were given 50 g protein, 50 g glucose, or 50 g glucose with 50 g protein as a single meal in random sequence. The plasma glucose and insulin response was determined over the subsequent 5 h. The plasma glucose area above the baseline following a glucose meal was reduced 34% when protein was given with the glucose. When protein was given alone, the glucose concentration remained stable for 2 h and then declined. The insulin area following glucose was only modestly greater than with a protein meal (97 +/- 35, 83 +/- 19 microU X h/ml, respectively). When glucose was given with protein, the mean insulin area was considerably greater than when glucose or protein was given alone (247 +/- 33 microU X h/ml). When various amounts of protein were given with 50 g glucose, the insulin area response was essentially first order. Subsequently, subjects were given 50 g glucose or 50 g glucose with 50 g protein as two meals 4 h apart in random sequence. The insulin areas were not significantly different for each meal but were higher when protein + glucose was given. After the second glucose meal the plasma glucose area was 33% less than after the first meal. Following the second glucose + protein meal the plasma glucose area was markedly reduced, being only 7% as large as after the first meal. These data indicate that protein given with glucose will increase insulin secretion and reduce the plasma glucose rise in at least some type II diabetic persons.

We have been interested in the metabolic effects of ingested fuels, both in normal subjects and in people with type 2 diabetes. Recently, we have become interested in the regulation of glucose production and the regulation of gluconeogenesis in particular. We are not aware of a recent comprehensive review of these topics. Therefore, we have reviewed the currently available literature. The pertinent papers obtained from a Medline search of the words gluconeogenesis, glycogenolysis, hepatic glucose output, as well as papers from our personal files, form the basis of this review. In order to analyse the data, it also was necessary to review the relevant methodology used in determining gluconeogenesis. Pathway diagrams have been included with this review in order to illustrate and highlight key aspects of the methodologies. Current data support the hypothesis that the rate of glucose appearance changes but the rate of gluconeogenesis remains remarkably stable in widely varying metabolic conditions in people without diabetes. In people with diabetes, whether gluconeogenesis remains unchanged is at present uncertain. Available data are very limited. The mechanism by which gluconeogenesis remains relatively constant, even in the setting of excess substrates, is not known. One interesting speculation is that gluconeogenic substrates substitute for each other depending on availability. Thus, the overall rate is either unaffected or only modestly changed. This requires further confirmation.